https://www.spg.pt/wp-content/uploads/2015/11/2015-CCR-hereditario.pdf

ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.

Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia characterized by telangiectases and arteriovenous malformations (AVMs) in particular locations described in consensus clinical diagnostic criteria published in 2000. Two genes in the transforming growth factor-beta (TGF-β) signaling pathway, ENG and ACVRL1, were discovered almost two decades ago, and mutations in these genes have been reported to cause up to 85% of HHT. In our experience, approximately 96% of individuals with HHT have a mutation in these two genes, when published (Curacao) diagnostic criteria for HHT are strictly applied. More recently, two additional genes in the same pathway, SMAD4 and GDF2, have been identified in a much smaller number of patients with a similar or overlapping phenotype to HHT. Yet families still exist with compelling evidence of a hereditary telangiectasia disorder, but no identifiable mutation in a known gene. Recent availability of whole exome and genome testing has created new opportunities to facilitate gene discovery, identify genetic modifiers to explain clinical variability, and potentially define an increased spectrum of hereditary telangiectasia disorders. An expanded approach to molecular diagnostics for inherited telangiectasia disorders that incorporates a multi-gene next generation sequencing (NGS) HHT panel is proposed.

/pdf/hereditary-hemorrhagic-telangiectasia-genetics-and-molecular-uratk7ebhj.pdf

Hereditary hemorrhagic telangiectasia: genetics and molecular diagnostics in a new era.

Vascular disorders of the liver, although affecting less than 5/10,000 patients, collectively account for a number of rare conditions that represent an important health problem worldwide in the field of liver diseases. A common characteristic of most of these disorders is that they can cause non-cirrhotic portal hypertension with an ensuing high morbidity and mortality. In addition, special relevance addresses the fact that patients are usually young with an otherwise normal life expectancy that may be markedly shortened if they are not adequately managed. Advances in the knowledge of vascular liver disorders are hampered by the small number of cases and a limited number of studies assessing natural history, pathophysiology or therapy. However, in recent years, interest for these disorders has increased as reflected in the rise in the number of publications on this topic. In addition, EASL has encouraged this increased interest by sponsoring a monothematic conference in June 2012 in Tallinn on vascular disorders of the liver, and by proposing an EASL clinical practice guidelines on the issue. These guidelines will not cover all possible vascular disorders of the liver but are mainly based on the subjects discussed during the monothematic conference; Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia and portal vein thrombosis in cirrhosis. Guidelines have been written according to published studies retrieved from Pubmed. The evidence and recommendations have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. The strength of evidence has been classified into three levels: high (A), moderate (B) or low quality (C), while the grade of recommendation in two levels: strong (1) or weak (2) (Table 1). The higher the quality of the evidence, the more likely a strong recommendation is warranted. Where no clear evidence existed, recommendations were based on agreed opinions of the writing committee members.

https://www.journal-of-hepatology.eu/article/S0168-8278(15)00547-4/pdf

EASL Clinical Practice Guidelines: Vascular diseases of the liver q

EASL Clinical Practice Guidelines : Vascular diseases of the liver European Association for the Study of the Liver

http://spiral.imperial.ac.uk/bitstream/10044/1/22167/2/Shovlin.%20Blood%20Reviews%202010.pdf

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Background HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults.

Objective The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease.

Methods The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches.

Results The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

https://jmg.bmj.com/content/jmedgenet/early/2009/06/29/jmg.2009.069013.full.pdf

J Spears

Papers

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia